Autonomic Dysfunction and Cholelithiasis in Patients with Cirrhosis AJAY CHAWLA, MD, LOVEEN PUTHUMANA, MD, and PAUL J. THULUVATH, MD Gallstones are seen in 33– 46% of patients with cirrhosis, and their prevalence is known to increase with the duration and severity of liver disease. We hypothesized that autonomic neuropathy may contribute to the formation of gallstones or gallbladder disease, as in diabetics with autonomic neuropathy, due to impaired gallbladder emptying. The objective of our study was to determine the prevalence of gallstones or gallbladder disease in cirrhotic patients with and without autonomic neuropathy. We determined autonomic function tests, gallstones, and other gallbladder disease in 123 (male 71) with varying severity of liver disease (Child classes: A, 40; B, 45; C, 35). In all, 54 patients had gallstones and an additional 22 patients had other gallbladder disease (cholecystitis, common bile duct stones, or debris). Autonomic neuropathy was seen in 97 patients (one abnormal test in 48 and two or more in 49). The prevalence of gallstones was similar in Child A (57%), Child B (64%), and Child C (63%) cirrhosis. The gallstones or gallbladder disease was not increased in women, blacks, diabetics, or alcoholic cirrhotics. The prevalence of gallbladder disease was increased in patients with autonomic neuropathy (51% vs 35%, P = 0.08); in patients with Child C cirrhosis, gallstones (P = 0.018) and gallbladder disease ( P = 0.03) were seen more commonly in patients with autonomic neuropathy. Our findings suggest that autonomic neuropathy may contribute to the formation of gallstones in patients with advanced cirrhosis, perhaps by impairing gallbladder and sphincter of Oddi dysmotility. KEY WORDS: cirrhosis; autonomic dysfunction; cholelithiasis. Gallstones, predominantly pigmented, are seen in 33– 46% of patients with chronic liver diseases (1–12). The yearly incidence of cholelithiasis in patients with cirrhosis ranges from 2% to 4.7% in prospective, ultrasound studies (3, 5, 6). In one study, the cumu- lative probability of stone formation was 6.5% at 2 years, 18.6% at 4 years, 28.2% at 4 years, and 40.9% at 6 years (6). It has been suggested that the preva- lence of gallstones increases with the duration as well as the severity of the liver diseases (3–5). The etiology of liver disease may also determine the prevalence of cholelithiasis. Alcoholism is considered to be an in- dependent risk factor for cholelithiasis in some stud- ies (3, 5). In one study, patients with alcoholic cirrho- sis had about 10 times higher incidence of gallstones compared to patients who had cirrhosis from viral hepatitis (3). The other risk factors that have been reported include female sex, ascites, age, family his- tory of gallstones, and high body mass index (BMI) (6, 10, 12). However, these findings are not consistent. The gallstone formation in liver disease is most likely multifactorial. The proposed mechanism in- cludes hemolysis, changes in bile constituents, an increase in estrogen levels, and changes in gallbladder and sphincter of Oddi motility (1, 3, 13–19). A low ratio of bile salt to unconjugated bilirubin and high levels of monoconjugated bilirubin were associated with a higher incidence of pigmented stones in pa- tients with cirrhosis in one study (14). It has been Manuscript received June 19, 2000; accepted October 24, 2000. From the Department of Medicine, The Johns Hopkins Univer- sity School of Medicine Baltimore, Maryland 21205. Address for reprint requests: Dr. Paul J. Thuluvath, The Johns Hopkins Hospital, Room 429, 1830 Building, 1830 E. Monument Street, Baltimore, Maryland 21205. Digestive Diseases and Sciences, Vol. 46, No. 3 (March 2001), pp. 495– 498 495 Digestive Diseases and Sciences, Vol. 46, No. 3 (March 2001) 0163-2116/01/0300-0495$19.50/0 © 2001 Plenum Publishing Corporation